Growth in salicylate (SAL) increases the resistance of a number of Gram-negative bacteria to a variety of clinically important antibiotics. We have traced this effect in Escherichia coli to a reduction in the permeability of the outer membrane due to sharply reduced synthesis of OmpF, a major channel-forming outer membrane protein (porin). The transcription and translation of ompF and other relevant genes was studied by means of lacZ fusions, SDS gel electrophoresis of outer membrane proteins, and by measurements of outer membrane permeation. Growth in broth containing different concentrations of SAL reduced ompF-specific translation by as much as 99% (at 10 mM). However, ompF transcription was not affected by SAL. SAL decreases ompF translation in two ways. The first involves increasing micF transcription. Since micF transcripts are anti-sense to the 5' region of ompF transcripts, they decrease the translation of ompF mRNA by hybridizing with it. SAL increased micF transcription by 3- to 4-fold. In the absence of micF, the effect of SAL on ompF translation was clearly diminished, showing that it plays an important role in decreasing the amounts of OmpF in the outer membrane. However, since a considerable effect of SAL on ompF translation was evident even in the absence of micF, we infer the existence of a second (unknown) mechanism that reduces ompF translation in response to SAL. In addition to affecting on ompF expression, growth in SAL increased the transcription of ompC, the gene for a second major porin. This was particularly obvious in the case of certain regulatory mutants that have very low levels of ompC transcription when grown without SAL. Since micF and ompC are divergently transcribed from a sequence that lies between them, we have proposed that growth in SAL specifically facilitates the joint transcription of micF and ompC.